TY - JOUR
T1 - Human Prostate-Specific Antigen Carries N-glycans with Ketodeoxynononic Acid
AU - Wang, Wei
AU - Zhang, Tao
AU - Nouta, Jan
AU - van Veelen, Peter A.
AU - de Haan, Noortje
AU - de Reijke, Theo M.
AU - Wuhrer, Manfred
AU - Lageveen-Kammeijer, Guinevere S. M.
N1 - Funding Information: The authors would like to thank Arnoud de Ru, George M.C. Janssen, Carolien A.M. Koeleman, and Irina Dragan for their contributions to this study. This research was supported by the Chinese Scholarship Council, Cure for Cancer Foundation and Astellas Pharma B.V. Wei Wang performed the experiments and data analysis. Tao Zhang performed the experiments and data analysis regarding PGC-nanoLC–MS. Jan Nouta and Guinevere S.M. Lageveen-Kammeijer performed the experiments regarding the clinical cohort. Peter A. van Veelen provided the Orbitrap measurements. Wei Wang, Manfred Wuhrer, and Guinevere S.M. Lageveen-Kammeijer conceptually designed the work. and wrote the manuscript. All authors read and commented on the manuscript. Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, and Guinevere S.M. Lageveen-Kammeijer declare that they have no conflict of interest or financial conflicts to disclose. The raw mass spectrometric data files that support the findings of this study and the clinical cohort data files are available in MassIVE in .mzXML format, with the identifier MSV000089140 [https://doi:10.25345/C5BG2HF07]. All other data supporting the findings of this study are available from the corresponding author on request. Funding Information: The authors would like to thank Arnoud de Ru, George M.C. Janssen, Carolien A.M. Koeleman, and Irina Dragan for their contributions to this study. This research was supported by the Chinese Scholarship Council, Cure for Cancer Foundation and Astellas Pharma B.V. Publisher Copyright: © 2023 THE AUTHORS
PY - 2023/7
Y1 - 2023/7
N2 - Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans.
AB - Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans.
KW - Glycosylation
KW - Kdn
KW - Ketodeoxynononic acid
KW - Prostate cancer
KW - Prostate-specific antigen
UR - http://www.scopus.com/inward/record.url?scp=85165066228&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.eng.2023.02.009
DO - https://doi.org/10.1016/j.eng.2023.02.009
M3 - Article
SN - 2095-8099
VL - 26
SP - 119
EP - 131
JO - Engineering
JF - Engineering
ER -